Binding affinities of N2-substituted-indazole-3-acylsulfonamides to MCL-1, BCL-2 and BCL-xL. NA = no activity.
| |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Compound number | R2 | K i (μM) | Compound number | R2 | K i (μM) | ||||
| MCL-1 | BCL-2 | BCL-xL | MCL-1 | BCL-2 | BCL-xL | ||||
| 14a |
|
1.20 ± 0.17 | 0.51 ± 0.10 | >10 | 14k |
|
2.30 ± 0.17 | 0.90 ± 0.25 | 6.66 ± 3.14 |
| 14b |
|
1.32 ± 0.16 | 0.53 ± 0.09 | 7.99 ± 2.43 | 14l |
|
1.68 ± 0.33 | 0.96 ± 0.08 | >10 |
| 14c |
|
1.61 ± 0.10 | 0.42 ± 0.16 | NA | 14m |
|
2.16 ± 0.61 | 0.84 ± 0.23 | >10 |
| 14d |
|
1.30 ± 0.11 | 0.57 ± 0.09 | >10 | 14n |
|
1.95 ± 0.18 | 0.71 ± 0.11 | 7.41 ± 2.56 |
| 14e |
|
1.28 ± 0.15 | 0.62 ± 0.14 | 3.40 ± 1.19 | 14o |
|
1.00 ± 0.10 | 1.22 ± 0.50 | >10 |
| 14f |
|
1.57 ± 0.14 | 0.60 ± 0.11 | 3.45 ± 0.73 | 14p |
|
1.46 ± 0.13 | 0.46 ± 0.05 | >10 |
| 14g |
|
1.12 ± 0.07 | 1.18 ± 0.14 | 4.42 ± 0.53 | 14q |
|
1.36 ± 0.21 | 0.71 ± 0.25 | >10 |
| 14h |
|
1.46 ± 0.13 | 0.46 ± 0.05 | >10 | 14r |
|
1.42 ± 0.11 | 0.77 ± 0.18 | NA |
| 14i |
|
1.65 ± 0.18 | 1.52 ± 0.31 | >10 | 1 | — | 0.247 ± 0.03 | 1.20 ± 0.16 | >10 |
| 14j |
|
1.77 ± 0.29 | 0.66 ± 0.18 | >10 | ABT-737 | — | NA | <0.04 | <0.04 |
| S63845 | — | 0.039 ± 0.01 | NA | NA | |||||